کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
5888754 1568127 2016 9 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Full Length ArticleEffect of combined treatment with zoledronic acid and parathyroid hormone on mouse bone callus structure and composition
ترجمه فارسی عنوان
مقادیر طول کامل اثر درمان ترکیبی با اسید زولدرونیک اسید و هورمون پاراتیروئید بر ساختار و ترکیب کالوس استخوان موش
کلمات کلیدی
بهبود استخوان، کیفیت استخوانی، اسید زولدرونیک، هورمون پاراتیروئید، توموگرافی کامپیوتری میکروسکوپی، طیف سنجی رامان،
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی زیست شناسی تکاملی
چکیده انگلیسی


- We compared the effects of parathyroid hormone, zoledronic acid and their combination in a mouse closed fracture model
- We applied micro-computed tomography, Raman spectroscopy, quantitative histomorphometry, and deconvolution microscopy.
- We found differences at all structural levels in the treatment groups but no changes in material composition between all groups
- PTH mono-treatment showed a significant increase in lacuna volume opening questions on the mechanism of osteocytic osteolysis

In recent years, great interest in combined treatment of parathyroid hormone (PTH) with anti-resorptive therapy has emerged. PTH has been suggested to aid bridging of atrophic fractures and improve strength in closed fracture models. Bisphosphonate treatments typically result in a larger woven bone callus that is slower to remodel. The combination of both drugs has been demonstrated to be effective for the treatment of osteoporotic bone loss in many preclinical studies. However, the effect of combined treatment on fracture repair is still largely unexplored. In this study, we aimed to compare these drugs as single-agent and in combination in a murine closed fracture model. We wanted to assess potential differences in material properties, morphometry and in the development of the lacuno-canalicular network. A total of 40 female, 11-week-old wild type mice underwent a closed fracture on the midshaft of the tibia and were assigned to four groups (n = 8-10 per group). Beginning on post-operative day 8, animals received different subcutaneous injections. Group 1 received a single injection of saline solution and Group 2 of zoledronic acid (ZA). Group 3 received daily dosing of PTH. Group 4 received a dual treatment, starting with a single dose of ZA followed by daily injection of PTH. Three weeks after fracture, all animals were euthanized and tibiae were assessed using micro-computed tomography (micro-CT), high-resolution micro-CT (HR micro-CT), Raman spectroscopy, quantitative histomorphometry, and deconvolution microscopy (DV microscopy). Combined treatment showed a significant increase of 41% in bone volume fraction and a significant decrease of 61% in the standard deviation of the trabecular spacing compared to vehicle, both known to be strong predictors of callus strength. An analysis via HR micro-CT showed similar results on all groups for lacunar numerical density, whereas mean lacuna volume was found to be higher compared to vehicle in treated groups, but only PTH mono-treatment showed a significant increase compared to vehicle (+ 45%). Raman spectroscopy did not reveal detectable changes in material properties of the bone calluses. Sclerostin staining, tartrate resistant acid phosphatase (TRAP) staining and canalicular analysis with DV microscopy on a subset of samples did not display distinctive difference in any of the treatments.We therefore consider PTH + ZA treatment beneficial for bone healing. No clear negative effect on bone quality was detected during this study.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Bone - Volume 92, November 2016, Pages 70-78
نویسندگان
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